What are the steps for diagnosing Hepatitis C Virus (HCV) infection?

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Last updated: February 12, 2025View editorial policy

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From the Guidelines

Diagnosing Hepatitis C Virus (HCV) infection involves a step-by-step approach. The first step is to test for HCV antibody using either a rapid or laboratory-conducted assay, which can indicate current or past HCV infection, or false positivity 1.

Steps for Diagnosing HCV Infection

  • Initial Testing for HCV Antibody: An FDA-approved test for HCV antibody should be used, with outcomes reported as reactive or nonreactive 1.
  • Testing for HCV RNA: If the HCV antibody test is reactive, an FDA-approved NAT assay should be used to detect HCV RNA in serum or plasma, indicating current HCV infection 1.
  • Reflex Testing: Reflex testing, where HCV RNA is tested in the same sample as the HCV antibody test, can increase the proportion of patients who receive subsequent linkage to care 1.
  • Point-of-Care Tests: Point-of-care tests, such as antibody detection in saliva or RNA detection via fingerstick blood sampling, can provide quick and accessible results, especially in settings with limited resources 1.
  • Dried Blood Spot Testing: Dried blood spot testing can facilitate sample collection and simultaneous screening for co-infections, such as HIV 1.

Special Considerations

  • Immunocompromised Patients: For patients who are immunocompromised, testing for HCV RNA can be considered, as anti-HCV may not be detectable in these patients 1.
  • Recent Exposure: For persons who might have been exposed to HCV within the past 6 months, testing for HCV RNA or follow-up testing for HCV antibody is recommended 1.
  • False-Positive Results: False-positive results for anti-HCV can occur, and HCV RNA testing is necessary to confirm the diagnosis 1.

From the Research

Steps for Diagnosing Hepatitis C Virus (HCV) Infection

The diagnosis of HCV infection involves several steps, including:

  • Initial screening using serological assays to detect anti-HCV antibodies in the patient's serum or plasma 2, 3
  • Confirmatory testing using molecular assays, such as qualitative and quantitative HCV RNA tests, to detect the presence of the virus and determine viral load 2, 3
  • Genotyping to identify the dominant strain of the virus, which is essential for guiding treatment 2, 3
  • Additional biomarker assays to assess liver function and enable disease staging 3

Laboratory Diagnostic Tests

Specific laboratory diagnostic tests for HCV infection can be categorized into two main types:

  • Serological antibody tests, which detect anti-HCV in serum or plasma 2, 4
  • Molecular tests, which detect HCV RNA genome, investigate viral load, and determine the characteristics of the genome 2, 3, 4

Strategies for Diagnosis

Strategies for diagnosis and monitoring of HCV infection vary depending on the setting and goal:

  • In low-risk settings, such as blood banks, a positive anti-HCV result should be confirmed with an analytical antibody test, followed by a HCV RNA test 2
  • In high-risk populations or situations where HCV infection is suspected, a positive anti-HCV result is likely to be true positive, and confirmation with a HCV RNA test is significant 2
  • Quantitative HCV RNA testing and genotyping should be performed if therapy is considered 2

Recent Advancements

Recent studies have developed novel diagnostic assays, such as the HCV antigens enzyme immunoassay (HCV-Ags EIA), which can detect HCV infection in one step with high sensitivity and specificity 5 Additionally, advancements in hepatitis C diagnostics and the US regulatory landscape have created opportunities to improve hepatitis C diagnosis and include viral-first testing strategies 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis of hepatitis C virus (HCV) infection and laboratory monitoring of its therapy.

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2001

Research

Diagnosis and Management of Hepatitis C Virus Infection.

Journal of laboratory automation, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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